Human Muscle Tissues
By the end of 2nd or 3rd week of embryonic development, some cells of the ectoderm proliferate inward to become primitive streak. Then the cells of primitive streak start to rapidly grow and form mesoderm, from which three main group of human muscle tissues (skeletal muscle, cardiac muscle and smooth muscle) are gradually differentiated and shaped up during the following months.
Skeletal Muscle
Skeletal muscle consists of muscle fibers, i.e. bundles of 1 to 40 mm long, cylindrical and multinucleated muscle cells with a diameter of 10 to 100 μm. Oval nuclei are usually found under the membrane of the muscle cells. Skeletal muscles are mainly attached to skeletal bones to carry out rapid and forceful but discontinuous voluntary contraction for various movements of the body, although some contractions are also seen in viscera, such as diaphragm. As observed with light microscope, longitudinally sectioned muscle cells or fibers show cross-striations of alternating light and dark bands. The darker bands are called A bands with width of 1.5 μm, which are anisotropic, i.e. birefringent in polarized light, at mid A band, there is a less dark area, i.e. H band, which is bisected by a darker middle line, i.e. M line. The lighter bands, called I bands, 0.8 to 1.5 μm in width, are isotropic, i.e. they do not alter polarized light. Each I band is bisected by a dark transverse line, the Z line.
The smallest repetitive functional subunit of the contractile apparatus is called sarcomere, which extends from Z line to Z line, and about 2˜3 μm long in resting muscle. The sarcoplasm is filled with long cylindrical filamentous bundles called myofibrils, which have a diameter of 1˜2 μm and run parallel to the long axis of the muscle fiber, consisting of an end-to-end chain-like arrangement of sarcomeres. Laterally, it exhibits a characteristic pattern of transverse striations. This sarcomere pattern is mainly due to the presence of two types of filaments, thick and thin, that are lying parallel to the long axis of the myofibrils in a symmetric pattern. The thick filaments are 1.6 μm long and 15 nm wide, occupying the A band, i.e. the central portion of the sarcomere. The thin filaments, which are 1.0 μm long and 8 nm wide, run between and parallel to the thick filaments and have one end attached to Z line. As a result of this arrangement, the I bands consist of the portion of the thin filaments that do not overlap the thick filaments. The A bands are composed mainly of thick filaments in addition to portions of overlapping thin filaments. H bands are less dark zones in the center of band A, which corresponds to a region consisting only of the rod-like portion of the myosin molecules. Bisecting the H band is the M line, i.e. a region where lateral connections are made between adjacent thick filaments. The major protein of the M line is creatine kinase, which catalyzes the transfer of a phosphate group from phosphocreatine to ADP necessary for the production of ATP, thus providing the supply of ATP necessary for muscle contraction.
Striated muscle filaments contain four main proteins: actin, tropomyosin, troponin and myosin. Thin filaments are composed of the first three proteins, whereas thick filaments consist primarily of myosin.
Cardiac Muscle (Myocardium)
One special striated muscle, muscle cells are about 15 μm in diameter and 80˜100 μm in length, each cardiac muscle cell possesses only one or two centrally located pale-staining nuclei and distributed only in the heart, cross striations may be seen under light microscope. During embryonic development, cardiac muscle cells form complex junctions between their extended processes, making cells within a chain often bifurcate, or branch, and bind to cells in adjacent chains. In addition, a unique distinguishing character of cardiac muscle is presence of dark-staining transverse lines that cross the chains of cardiac cells at irregular intervals, named intercalated disks. These disks represent junctional complexes found at the interface between adjacent cardiac muscle cells, so as to prevent cells from pulling apart under constant contractile activities and provide ionic continuity between adjacent cells, allowing the signal to contract to pass in a wave from cell to cell. Consequently, heart consists of tightly knit bundles of cells, interwoven in a fashion that provides for a characteristic wave of contraction that leads to a wringing out of the heart ventricles. It can perform continuous, quick and strong contraction, functioning as a center pump of circulation system, which is not controlled by will, but which belongs to non-voluntary muscle.
The structure and function of the contraction proteins in cardiac cells are virtually the same as in skeletal muscle. The T-tubule system and sarcoplasmic reticulum, however, are not as regularly arranged in the cardiac myocytes. The T tubules are more numerous and larger, but sarcoplasmic reticulum is not as well developed in ventricular muscle than in skeletal muscle. Cardiac muscle cells contain numerous mitochondria, which occupy 40% or more of the cytoplasmic volume, reflecting the need for continuous aerobic metabolism in heart muscle. By comparison, only about 2% of skeletal muscle fibers are occupied by mitochondria. Fatty acids, transported to cardiac muscle cells by lipoproteins, are the major fuel of the heart.
Smooth Muscle
Smooth muscle is composed of elongated fusiform non-striated cells, ranging in size from 20 μm to 500 μm, each cell has a single nucleus located in the center of the broadest part of the cell. Each of the cells is enclosed by a basal lamina and a network of reticular fibers, which serve to combine the force generated by each smooth muscle fiber into a concerted action, e.g. peristalsis in the intestine. A rudimentary sarcoplasmic reticulum is present, similar to that of striated muscle, but find no T tubules in smooth muscle cells. They are major constituents in the walls of hollow visceral organs, such as bronchial tree, alimentary canal, biliary tract, urinary tract, vasculatures, uterus, and so on. It may perform slow and sustained contraction, carrying out their functions respectively. Smooth muscle also belongs to non-voluntary muscle.
The characteristic contractile activity of smooth muscle is related to the structure and organization of its actin and myosin filaments, which do not exhibit the paracrystalline organization present in striated muscles. In smooth muscle cells, bundles of myofilaments crisscross obliquely through the cell, forming a lattice-like network. These bundles consist of thin filaments (5 to 7 nm) containing actin and tropomyosin, and thick filaments (12 to 16 nm) containing myosin. Both structural and biochemical studies reveal that smooth muscle actin and myosin contract by a sliding filament mechanism similar to that occurring in striated muscles.
An influx of Ca2+ is involved in the initiation of contraction in smooth muscle. Ca2+, however, interacts with actin only when the myosin light chain is phosphorylated. For this reason, and because the tropomyosin complex of skeletal muscle is absent, the contraction mechanism of smooth muscle differs somewhat from skeletal and cardiac muscle. Ca2+ binds with calmodulin, a calcium-binding protein, to form Ca2+-calmodulin complex. The Ca2+-calmodulin complex activates myosin light chain kinase, the enzyme responsible for the phosphorylation of myosin light chain. Contraction or relaxation of smooth muscle may be regulated by hormones via cyclic AMP (cAMP). When a level of cAMP increases, myosin light-chain kinase is activated, myosin light chain is phosphorylated, and the cell contracts. A decrease in cAMP has the opposite effect, reducing contractibility.
Smooth muscle cells have an elaborate array of 10 nm intermediate filaments, coursing through their cytoplasm. Desmin (skeletin) has been identified as the major protein of intermediate filaments in all smooth muscles, and vimentin is an additional component in vascular smooth muscle. Two types of dense bodies appear in smooth muscle cells. One is membrane associated, the other is cytoplasmic. Both contain α-actinin and are thus similar to the Z lines of striated muscles. Both thin and intermediate filaments insert into dense bodies that transmit contractile force to adjacent smooth muscle cells and their surrounding network of reticular fibers.
Smooth muscle usually has spontaneous activity in the absence of nervous stimuli. Nervous stimuli have thus the function of modifying activity of the smooth muscle rather than, as in skeletal muscle, initiating it.
Mechanisms of Muscle Contraction
Skeletal Muscle Contraction
Skeletal muscle contraction involves the following processes:                a) a neuro-impulse for a movement starts from the central nervous system. The neuro-impulse is then transmitted along motor nerve fibers (axons) and reaches the motor end-plate (myoneural junction);        b) a neurotransmitter, acetylcholine, is released from the axon terminals;        c) the released acetylcholine binds to acetylcholine receptors in the sarcolemma at the junctional folds;        d) binding of the neurotransmitter makes the sarcolemma more permeable to sodium, resulting in membrane depolarization at the motor end-plate;        e) the depolarization is propagated along the surface of the muscle cells and deep into the muscle fibers via the triad, T tubule system; and        f) the depolarization signal is passed to the sarcoplasmic reticulum (SR), and induces Ca2+ release from SR cistern, which initiates the contraction cycle as the following mechanisms:                    (i) high concentration Ca2+ ions (10−5 M) within the sarcoplasmic reticulum cistern are passively released into the vicinity of the overlapping thick and thin 2+filaments, increasing the Ca ion concentration locally (10−6 to 10−7 M);            (ii) the Ca2+ ions bind to TnC subunit of troponin, the signal is immediately transmitted to tropomyosin by TnI subunit, and induces myosin-ATP to be converted into an active complex;            (iii) the spatial configuration of the three troponin subunits changes and drives the tropomyosin molecule deeper into the groove of the actin helix, so as to expose the myosin-binding site on the actin components, making actin free to interact with the head of the myosin molecule;            (iv) the head of myosin molecule interacts with actin at the binding site, resulting in formation of actin-myosin cross-bridge. The actin-myosin ATPase is activated, degrading ATP into ADP and Pi with a release of bio-energy, required for movement of muscle molecular motor—a deformation, or bending, of the head and a part of the rod-like portion of the myosin;            (v) The movement of the myosin head pulls the actin filaments (thin filaments) to slide over the myosin filaments (thick filaments), drawing the thin filaments further into the A band; and            (vi) The actin-myosin cross-bridge binds a new ATP molecule causing detachment of the bridge, resetting the myosin head reset for another contraction cycle (If no ATP available, the actin-myosin bridge becomes stable, accounting for the extreme muscular rigidity that occurs after death).                        
Although a large number of myosin heads extend from the thick filaments, at any one time during the contraction, only a small number of heads align with available actin-binding sites. As the bound myosin heads move the actin, the movement provides for more actin-binding sites available for alignment of new actin-myosin bridges. A single muscle contraction is the result of hundreds of cycles of actin-myosin cross-bridge-forming, sliding, and bridge breaking. The contraction activity that leads to a complete overlap between thin and thick filaments continues until Ca2+ ions are removed and the troponin-tropomyosin complex again covers the myosin binding site at actin molecule. During contraction, the I band decreases in size as thin filaments penetrate into the A band. The H band—the part of the A band with only thick filaments—diminishes in width as the thin filaments completely overlap the thick filaments. A net result is that each sarcomere, and consequently the whole muscle cell, is greatly shortened, although there is no change in length of both thin and thick filaments themselves.
Cardiac Muscle Contraction
The rhythmic cardiac muscle contraction is initiated by self-generated rhythmic impulses, which normally starts from nodus sinuatrialis, then is transmitted along atrial muscle fibers and cardiac conductive system, which consists of nodus atrioventricularis, fasciculus atrioventricularis (His fasciculus), crus sinistrum, crus dextrum and Purkinje fibers, finally reaches to ventricular muscle fibers. Meanwhile, the impulse sequentially results in depolarization of atrial cardiac muscle, then ventricular cardiac muscle. The events following the depolarization to cause cardiac muscle contraction are similar to those occurring in skeletal muscle, i.e. Ca2+ release, recycling of actin-myosin filament cross-bridge formation, and sliding movement.
In addition, there is rich autonomic nerve supply to cardiac muscles, so that both sympathetic and parasympathetic nervous impulses may apparently modify activities of cardiac muscle contraction.
Smooth Muscle Contraction
Smooth muscles are non-voluntary muscles. They may spontaneously contract but the contraction is slow and sustained. Many factors, such as mechanical stimuli, physical factors, chemicals, hormones, neurotransmitters and so on, may substantially influence smooth muscle contraction. Generally smooth muscle contraction occurs as follows:                a) an initial factor firstly causes Ca2+ influx into smooth muscle cells, or induces intra-cellular Ca2+ release from sarcoplasmic reticula (SR);        b) The Ca2+ combines with a calcium binding protein, such as calmodulin, to form Ca2+-protein (Ca2+-calmodulin) complex;        c) The Ca2+-protein complex activates myosin light chain kinase (MLCK);        d) The myosin light chain kinase (MLCK) catalyzes phosphorylation of myosin light chain (MLC);        e) The phosphorylated myosin light chain activates actin-myosin ATPase; and        f) The activated actin-myosin ATPase catalyzes hydrolysis of ATP, resulting in release of bio-energy for smooth muscle contraction.        
The subsequent events, i.e. the mechanism of smooth muscle actin-myosin interaction, recycling of actin-myosin cross-bridge formation, thin and thick filament sliding, are similar to those occurring in a skeletal muscle contraction.
It would be highly desirable to be provided with a new muscle relaxant for smooth and cardiac muscles.